Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1

ABSTRACT: Metabolic programs and host defense are highly integrated to ensure proper immune responses during stress. Central to these responses, mTOR regulates immune functions by sensing and integrating environmental cues, yet how these systems are coordinated at the intestinal surface remains undefined. We show that the antimicrobial peptide α-defensin is functionally sustained during nutrient deprivation due to regulation of defensin-processing enzyme MMP7 by microbiota- and host-derived factors. Unlike other antimicrobial peptides, the MMP7-α-defensin axis remains active during nutrient fluctuations, providing essential protection against enteric pathogens. Sustained Mmp7 expression requires the microbiota and is mediated by de-repression of the transcription activator Atoh1 upon attenuation of the transcriptional repressor Hes1 in intestinal epithelial cells. Hes1 levels are regulated via mTOR and controlled translationally, constituting a metabolism-translation-transcription loop. Disrupting this loop by supplying nutrients paradoxically compromises anti-bacterial defense. Together, these results uncover a regulatory circuit that couples host nutrient status to epithelial anti-microbial immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE119568 | GEO | 2019/03/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A Gram-positive three-component antimicrobial peptide-sensing system

Project description:To survive during colonization or infection of the human body, microorganisms must defeat antimicrobial peptides, which represent a key component of innate host defense in phagocytes and on epithelia. However, is not known how the clinically important group of Gram-positive bacteria sense antimicrobial peptides to coordinate a directed defensive response. By determining the genome-wide gene regulatory response to human beta defensin 3 in the nosocomial pathogen Staphylococcus epidermidis, we discovered an antimicrobial peptide sensor system that controls major specific resistance mechanisms to antimicrobial peptides and is unrelated to the Gram-negative PhoP/PhoQ system. Wild type untreated in triplicate is compared to wild type treated in triplicate along with three mutants in triplicate with and without treatment of human beta defensin 3, totalling 30 samples

2010-05-26 | E-GEOD-7163 | biostudies-arrayexpress

Single-cell RNA sequencing and total RNA sequencing data, respectively, evaluating the expression of selective genes from C57BL/6 mouse-derived small intestinal organoids and whole ileal tissue from naïve Il22Ra1fl/fl;Defa6-cre+/- mice

Project description:All intestinal epithelial lineages express the IL-22 receptor; however, it is not known whether IL-22-dependent regulation of small intestinal host defense is dependent on ISCs or a specific epithelial lineages. To examine differences in gene expression among small intestinal enterocytes, single cell RNA sequencing was performed on primary small intestinal organoids derived from naïve C57BL/6 mice. Our scRNA-seq results demonstrate that Paneth cells express the highest level of Il22ra1 when compared to ISCs as well as enterocyte, goblet, tuft, and endocrine lineages. Additionally, total RNA sequencing (RNA-seq) of the terminal ileum of naïve Il22Ra1fl/fl;Defa6-cre+ (Paneth cell-specific IL22Ra1 knockout) and littermate cre- mice was performed. Our sequencing data revealed reduced expression of Paneth cell-specific Lyz1, Mmp7, and select alpha-defensin antimicrobial peptides but increased expression of IL-22 inducible Reg3g and serum amyloid genes (Saa1 and Saa3) in the terminal ileum of naïve Il22Ra1fl/fl;Defa6-cre+ mice

2020-10-14 | GSE159423 | GEO

A Gram-positive three-component antimicrobial peptide-sensing system

2008-02-26 | GSE7163 | GEO

Loss of L-cells due to acute graft-versus-host disease leads to Paneth cell defects which can be compensated by glucagon like peptide-2

Project description:Paneth cells are targets of allo-reactive T cells during acute graft-versus-host disease (GVHD). GVHD-related loss of Paneth cells is connected to intestinal dysbiosis and a decline of antimicrobial peptides. Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone, produced by the intestinal L-cells, that leads to expansion of Paneth cells. Microarray-based analysis of the intestinal tract revealed upregulation of a host-defense gene signature, increased Reg3-γ and Defensin-α-4 in the teduglutide treated group compared to the vehicle treated group. these results indicate that treatment of GVHD mice the GLP-2 analogue, teduglutide, restores intestinal homeostasis with increased Paneth cells and antimicrobial peptides

2023-10-29 | GSE138439 | GEO

The commensal-derived metabolite butyrate imprints an antimicrobial program in macrophages

Project description:The balance between tolerogenic and inflammatory responses determines immune homeostasis in the gut. Dysbiosis and a defective host defense against invading intestinal bacteria can shift this balance via bacterial-derived metabolites and trigger chronic inflammation. We show that the short chain fatty acid butyrate modulates monocyte to macrophage differentiation by promoting antimicrobial effector functions. The presence of butyrate modulates antimicrobial activity via a shift in macrophage metabolism and reduction in mTOR activity. This mechanism is furthermore dependent on the inhibitory function of butyrate on histone deacetylase 3 (HDAC3) driving transcription of a set of antimicrobial peptides including calprotectin. The increased antimicrobial activity against several bacterial species is not associated with increased production of conventional cytokines. Butyrate imprints antimicrobial activity of intestinal macrophages in vivo. Our data suggest that commensal bacteria derived butyrate stabilize gut homeostasis by promoting antimicrobial host defense pathways in monocytes that differentiate into intestinal macrophages.

2019-01-30 | GSE111049 | GEO

Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1

Project description:Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1

| PRJNA489601 | ENA

Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1

Project description:Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1

| PRJNA489606 | ENA

Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1

Project description:Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1

| PRJNA489608 | ENA

Neutrophil-specific defensin receptors prevent skin dysbiosis and bacterial infection

Project description:Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. In this study, we discovered that epithelium-derived antimicrobial peptides defensins activate orphan GPCRs Mrgpra2a/b on neutrophils. This signaling axis is required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated two mutant mouse lines, Defensin conditional knockout (Def cKO, K14-cre; Def fl/fl) in which the entire Def gene cluster is conditionally deleted from keratinocytes, and Mrgpra2 double knockout (Mrgpra2 dKO). We used high-throughput RNA sequencing to evaluate the whole transcriptomes of WT and mutant animals' skin under naive condition and 24 hours post-S. aureus infection. Disruption of defensin-Mrgpra2 signaling caused reduction of a network of pro-inflammatory and antibacterial gene expression. This study demonstrates the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.

2021-10-01 | GSE178507 | GEO

Colonic Gene expression of SPF mice fed either a Control Diet or a High Salt Diet

Project description:Compositional changes in the microbiota (dysbiosis) may be a basis for Irritable Bowel Syndrome (IBS) but biomarkers are currently unavailable to direct microbiota-directed therapy. We therefore examined whether changes in fecal β-defensin could be a marker of dysbiosis in a murine model. Experimental dysbiosis was induced using four interventions relevant to IBS: a mix of antimicrobials, westernized diets (high-fat/high-sugar and, high salt diets), or mild restraint stress. Fecal mouse β-defensin-3 and 16S rRNA-based microbiome profiles were assessed at baseline, during and following these interventions. Each intervention, except for mild restraint stress, altered compositional and diversity profiles of the microbiota. Exposure to antimicrobials or a high-fat/high-sugar diet, but not mild restraint stress, resulted in decreased fecal β-defensin-3 compared to baseline. In contrast, exposure to the high salt diet increased β-defensin-3 compared to baseline but this was not accompanied by discernible inflammatory changes in the host.

2023-07-11 | GSE225272 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data